PD1/PDL1阻断治疗因其独特的肿瘤微环境免疫调控功能在多种肿瘤临床试验中疗效显著，但应答率仅20%左右，即近80%的患者无应答，因此阐明决定其应答的机制和关键因素对于治疗效果的预判和联合治疗靶标的选择至关重要。我们前期研究发现在乳腺癌进展中CXCR2+MDSCs亚群在免疫系统和肿瘤局部显著扩增，促进肿瘤EMT转变，诱导CTL耗竭，加速肿瘤进展和转移；且在PD1/PDL1阻断治疗无效荷瘤小鼠中发现大量该亚群募集，上述结果提示该亚群与PD1/PDL1阻断治疗无效相关。本课题旨在此基础上，采用高通量筛选、活体成像、多光谱分析等平台，阐明该亚群在PD1/PDL1阻断治疗中的作用；明确该亚群是否可以作为PD1/PDL1治疗策略选择或疗效预判的靶标；联合阻断该亚群与PD1/PDL1能否显著延长生存期，以期为PD1/PDL1阻断在乳腺癌尤其三阴性乳腺癌的治疗提供参考，也为联合治疗靶标的选择提供方向。

The efficacy of PD1/PDL1 blockage in advanced tumor therapy has been significantly increased both in pre- and clinical trials by its specific regulative function on tumor microenvironment. However, the positive response ratio is approximately 20%, this means that there are nearly 80% patients who is non-response or resistant to PD1/PDL1 blocking treatment. Therefore, it is very important to identify the mechanisms of non-response or resistance, to find the key factors that control the positive response to anti-PD1/PDL1 for predicting therapeutic outcome, and to identify targets for combination therapy with PD1/PDL1 blockage. Our previous studies demonstrated that CXCR2+MDSCs could expand and recruit in spleen, blood, lymph node and tumor tissues, and promoted tumor cells epithelial mesenchymal transition (EMT), increased the immunosuppressive molecular such as PD1, PDL1, TIM3, LAG3, and LITAG expression in T cells and induced T cells exhaustion, resulting in inhibiting anti-tumor immune response and promoting tumor progression. Furthermore, in PD1/PDL1 blockage experiments, compared with positive response groups, there are more CXCR2+MDSCs and less CD4+T and CD8+T cells in system and local tumor microenvironment in non-response or resistant groups in breast cancer and ovarian cancer mice models. This project based on these studies and will further address the function of CXCR2+MDSCs in PD1/PDL1 blockade treatment, find the key factor(s) to control the positive response, whether combination with anti-PD1/PDL1 and key factor(s) inhibitor can prolong survival of tumor-bearing mice, inhibit or even regress tumor growth. These finding can offer value clues for application of PD1/PDL1 blockade in breast cancer, specifically in triple-negative breast cancer therapy, further provide orientation to make strategy for combination treatment.